bluebird bio Presents New Data for LentiGlobin Gene Therapy in
TransfusionDependent β-Thalassemia at 60th
Annual Meeting of the American Society of Hematology

First presentation of data from patients with a β0/β0
genotype and a pediatric patient treated with LentiGlobin in Phase 3
Northstar-3 study both have stopped chronic blood transfusions

10 of 11 patients with non-β0/β0
genotypes and more than three months follow-up have stopped chronic
transfusions in Phase 3 Northstar-2 study

Indicators of poor red blood cell production appear corrected in
exploratory analysis of bone marrow following treatment with LentiGlobin

December 03, 2018 09:15 PM Eastern Standard Time

CAMBRIDGE, Mass.--(BUSINESS WIRE)--bluebird
bio, Inc. (Nasdaq: BLUE) announced new data from the Phase 3
Northstar-2 (HGB-207) and Northstar-3 (HGB-212) clinical studies of its
investigational LentiGlobin™ gene therapy in the treatment of
patients with transfusion-dependent β-thalassemia (TDT) at the 60th
Annual Meeting of the American Society of Hematology (ASH).

“Our new data for LentiGlobin in transfusion-dependent β-thalassemia
includes a broader population of patients with both non-β0/β0
and β0/β0 genotypes, as well as our first
pediatric patients. In all of these patients we observed improved
hemoglobin levels and reduced or eliminated requirements for blood
transfusions following treatment with LentiGlobin,” said David Davidson,
M.D., chief medical officer, bluebird bio. “As our clinical studies
advance, we continue to gain insight into the therapeutic potential of
LentiGlobin across the spectrum of patients affected by TDT.”

TDT is an inherited blood disorder caused by a mutation in the β-globin
gene, which causes ineffective red blood cell production leading to
severe anemia. People with TDT require regular transfusions to maintain
hemoglobin (Hb) levels in order to survive, but chronic transfusions
carry risks, including iron overload that can result in multi-organ
damage and shortened life expectancy.

“In my practice, I see the serious complications of
transfusion-dependent β-thalassemia and the everyday toll this disease
takes on my patients and their families,” said Professor Franco
Locatelli, M.D., Ph.D., Full Professor of Pediatrics at the Sapienza
University in Rome, Chair of the Department of Pediatric Hematology and
Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy and lead
investigator for the Northstar-2 study. “Patients with
transfusion-dependent β-thalassemia are not able to make enough
hemoglobin to survive, which is why they need regular blood transfusions
every two to four weeks. After treatment with LentiGlobin, patients in
this Phase 3 study began to produce gene-therapy derived hemoglobin and
near-normal hemoglobin levels, which in the majority of patients
abrogated the need for blood transfusions.”

Northstar-2 (HGB-207) EfficacyAfter treatment with
LentiGlobin, patients are monitored for production of HbAT87Q,
which is gene therapy derived-hemoglobin. The production of HbAT87Q
increases the overall hemoglobin level in patients with the goal of
reducing or eliminating the need for transfusions.

Sixteen patients with non-β0/β0 genotypes (aged 8
– 34 years); two pediatric and 14 adolescents/adults with TDT have been
treated in the Phase 3 Northstar-2 study as of September 14, 2018, the
data cut-off date.

Eleven of these patients had at least three months of follow-up
available at the data cut-off. Ten of the 11 patients had stopped
receiving transfusions and had hemoglobin levels of 11.1 – 13.3 g/dL at
the time of the last study visit (3 – 18 months post-treatment). HbAT87Q
levels in these 10 patients ranged from 7.7 – 10.6 g/dL and
significantly contributed to total hemoglobin (67 – 92 percent).

An exploratory analysis was conducted with bone marrow from six patients
with 12 months of follow-up after treatment. The samples were evaluated
for cellularity and myeloid to erythroid ratio. A low myeloid to
erythroid ratio is a key feature of dyserythropoesis, or abnormal bone
marrow red blood cell production, characteristic of patients with TDT.
In five patients, all of who had stopped chronic transfusions, an
increase in the myeloid to erythroid ratio was observed, suggesting
improvement in red blood cell production.

Northstar-3 (HGB-212) EfficacyAs of September 14, 2018,
three patients with TDT and a β0/β0 genotype or an
IVS-I-110 mutation had been treated with LentiGlobin in the Phase 3
Northstar-3 study.

All three patients, as of November 19, 2018, had total hemoglobin of
greater than 10 g/dL at their last assessment, including a pediatric
patient. Patient 1 had no transfusions following LentiGlobin treatment
and their last assessment at month 12, Patient 2 had their last
transfusion 1.9 months post-treatment and last assessment at month six,
Patient 3 had their last transfusion at 1.4 months post-treatment and
last assessment at month three.

Northstar-2 and Northstar-3 SafetyIn the Northstar-2 and
Northstar-3 studies the safety profile of LentiGlobin gene therapy
remained generally consistent with myeloablative busulfan conditioning,
including serious adverse events (SAEs) of vaso-occlusive liver disease.
One SAE of grade 3 thrombocytopenia was reported and considered possibly
related to LentiGlobin.

As of the data cut-off date, September 14, 2018, a total of 37
pediatric, adolescents and adult patients with TDT and a non-β0/β0
or β0/β0 genotype, including patients with
IVS-I-110 mutations, have been treated with LentiGlobin in the
Northstar, Northstar-2 and Northstar-3 studies.

For more information about the ongoing clinical studies of LentiGlobin
in TDT visit www.northstarclinicalstudies.com or
clinicaltrials.gov and use identifier NCT02906202 for Northstar-2
(HGB-207) and NCT03207009 for Northstar-3 (HGB-212).

About Transfusion-Dependent β-ThalassemiaTDT is an
inherited blood disorder caused by a mutation in the β-globin gene,
which causes ineffective red blood cell production leading to severe
anemia. Supportive care for people with TDT consists of a lifelong
regimen of chronic blood transfusions to enable survival and suppress
symptoms of the disease, and iron chelation therapy to manage iron
overload that results from the transfusions.

Despite the availability of supportive care, many people with TDT
experience serious complications and organ damage due to underlying
disease and iron overload. By eliminating or reducing the need for blood
transfusions, the long-term complications associated with TDT may be
reduced.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been
successfully used to treat TDT and is currently the only available
option with the potential to correct the genetic deficiency in TDT.
Complications of allo-HSCT include a risk of treatment-related
mortality, graft failure, graft-versus-host disease (GvHD) and
opportunistic infections, particularly in patients who undergo
non-sibling matched allo-HSCT.

About LentiGlobinLentiGlobin is a one-time gene therapy
being studied as a potential treatment to address the underlying genetic
cause of TDT, which could eliminate or reduce the need for blood
transfusions.

bluebird bio’s clinical development program for LentiGlobin includes
ongoing studies around the world with sites
in Australia, Germany, Greece, France, Italy, Thailand, the United
Kingdom and the United States. For more information visit: www.northstarclinicalstudies.com or
clinicaltrials.gov using identifier NCT01745120.

In addition, bluebird is conducting a long-term safety and efficacy
follow-up study (LTF-303) for people who have participated in bluebird
bio-sponsored clinical studies of LentiGlobin for TDT and sickle cell
disease.

In October 2018, the European Medicines Agency (EMA) accepted the
company’s marketing authorization application (MAA) for LentiGlobin™
gene therapy for the treatment of adolescents and adults with TDT and a
non-β0/β0 genotype.

The EMA previously granted Priority Medicines (PRIME) eligibility and
Orphan Medicinal Product designation to LentiGlobin for the treatment of
TDT. LentiGlobin is also part of the EMA’s Adaptive Pathways pilot
program, which is part of the EMA’s effort to improve timely access for
patients to new medicines.

The U.S. Food and Drug Administration (FDA) also granted LentiGlobin
Orphan Drug status and Breakthrough Therapy designation for the
treatment of TDT.

Forward-Looking StatementsThis release contains
“forward-looking statements” within the meaning of the Private
Securities Litigation Reform Act of 1995, including statements regarding
the Company’s views with respect to the potential for its LentiGlobin
product candidate to treat transfusion-dependent ß-thalassemia, and the
Company’s expectations regarding the review, potential regulatory
approval and potential commercial launch of its LentiGlobin product
candidate in the United States and Europe. Any forward-looking
statements are based on management’s current expectations of future
events and are subject to a number of risks and uncertainties that could
cause actual results to differ materially and adversely from those set
forth in or implied by such forward-looking statements. These risks and
uncertainties include, but are not limited to, the risks that the
preliminary positive efficacy and safety results from our prior and
ongoing clinical trials of LentiGlobin will not continue or be repeated
in our ongoing or planned clinical trials of LentiGlobin, the risks that
the changes we have made in the LentiGlobin manufacturing will not
result in improved patient outcomes, risks that the current or planned
clinical trials of LentiGlobin will be insufficient to support future
regulatory submissions or to support marketing approval in the US and
EU, and the risk that any one or more of our product candidates, will
not be successfully developed, approved or commercialized. For a
discussion of other risks and uncertainties, and other important
factors, any of which could cause our actual results to differ from
those contained in the forward-looking statements, see the section
entitled “Risk Factors” in our most recent Form 10-Q, as well as
discussions of potential risks, uncertainties, and other important
factors in our subsequent filings with the Securities and Exchange
Commission. All information in this press release is as of the date of
the release, and bluebird bio undertakes no duty to update this
information unless required by law.